4- Hydroxy-l-proline

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

RN 33996-33-7 MF C HnNO MW 173.17 EINECS 251-780-6 CN trans-1 -acetyl-4-hydroxy-L-proline... 

The use of backbone-modified poly (amino acids) as biomaterials was first suggested by Kohn and Langer (17) who prepared a polyester from N-protected trans-4-hydroxy-L-proline, and a poly(itiuno-carbonate) from tyrosine dipeptide as monomeric starting material (12,18). 

A linkage involving 4-hydroxy-L-proline and L-arabinose has been detected in glycoproteins of plant origin, and it is also possible that L-cys-teine is part of a carbohydrate-protein linkage. Of the types of linkages just mentioned, which have been extensively discussed in reviews,2-9 only the first three have been the subject of synthetic studies, and it is this aspect of the work that will be discussed in the present Chapter. 

Pyrrolo[l,2-rf [l,2,4]triazinones 21 were synthesized from methyl ester of /ra j-4-hydroxy-L-proline 72. The synthetic route involved formation of hydrazones followed by cyclisation with orthoesters <1998BMC349>. Similar reactions have been developed with 3-benzylindole-2-carbohydrazides 73 in reaction with triethyl orthoformate, giving the corresponding ring systems indolo[l,2-r][ 1,2,4]triazin-4-oncs 74 <2004JHC7>. 

In plants a linkage between 4-hydroxy-L-proline and L-arabinose and in halobacteria a linkage between L-asparagine and D-Glucose/2-acetamido-2-deoxy-D-galactose has been reported. 

Among other enantioselective alkylations, a series of 3-aminopyrrolidine lithium amides (67 derived from 4-hydroxy-L-proline) have been used to induce high ee% in the addition of alkyllithiums to various aldehydes. Structure-activity relationships are identified, and the role of a second chiral centre (in the R group) in determining the stereochemistry of the product is discussed. 

Derivatives of the 2,5-diazabicyclo[2.2.1]heptaine ring system (bridged piperazines) have been prepared from 4-hydroxyprolines. In a multistep transformation from tra j-4-hydroxy-L-proline (the last step was cyclization with benzylamine) a mixture of diastereoisomers 71 was obtained and separated [92H(34)241]. In a similar manner, the methyl and oxo analogs were obtained [67AJC1493 92H(34)679]. The commercially available N-... 

Cbz-4-hydroxy-L-proline was used in the preparation of 72 (the Geissman-Waiss lactone), which is a synthon for necines (82H23). This compound was prepared in eight steps (62JOC139). The alkaloids retronecine, platy-necine, and croalbinecine were prepared from the lactone (83H1331). 

This enzyme [EC 5.1.1.8] catalyzes the interconversion of tran5 -4-hydroxy-L-proline to d5 -4-hydroxy-D-proline. It also interconverts rrans-4-hydroxy-D-proline and cis-4-hydroxy-L-proline. 

Several syntheses of the hepatatoxic alkaloid (+)-retronecine have been reported although the most succinct has utilized a chiral azomethine ylide cycloaddition to construct the bicychc skeleton. The ylide processor 175, which was obtained in five efficient steps from commercially available tran -(l )-4-hydroxy-L-proline, underwent double desilyation in the presence of AgF (described in detail in Section 3.1.1) and in situ cycloaddition with methyl propiolate, to deliver a 3 1 mixture of cycloadducts in favor of the desired regioisomer. DiisobutyMuminum (DIBAL) reduction of 176 furnished enantiopure (-F)-retronecine (Scheme 3.50). 

It has been shown that phosphorylation changes the local conformation of a protein and thereby affects the activity of the complete protein. 341 Phosphorylation of serine and threonine side chains often occurs (Scheme 2). Phosphoamino acids are readily characterized using 3H and 31P NMR experiments. The H and 31P NMR parameters are distinct for phosphorylated serine, threonine, and tyrosine and have also been used to identify both cis-and trans-O-phospho-4-hydroxy-L-proline. 35 Phosphorylation of Cys is rare, but it can be identified by NMR even in large proteins. 36 ... 

The pyrrolidine is prepared from 4-hydroxy-L-proline ethyl ester. Supplier Chemical Dynamics Corp., South Plainfields, N.J. 

Most papers deal with diethylzinc. Chiral (3/f,5/f)-dihydroxypiperidines (75), derived from trans-4-hydroxy-L-proline, give up to 98% ee in its additions to benzaldehyde and heptanal.212... 

Li Z, Huang L (2004) Sustained delivery and expression of plasmid DNA based on biodegradable polyester, poly(D,L-lactide-co-4-hydroxy-l-proline). J Control Release 98 437 146... 

Lim Y, Choi YH, Park J (1999) A self-destroying polycationic polymer biodegradable poly (4-hydroxy-L-proline ester). J Am Chem Soc 121 5633-5639... 

The number of synthetic routes to the natural 1-hydroxymethyl-pyrrolizidines continues to increase. Robins and Sakdarat have achieved the first synthesis of these necines in optically active form, using natural (-)-4-hydroxy-L-proline as a chiral template.2 The dihydropyrrolizine ester (2) was prepared by regiospecific 1,3-dipolar cycloaddition of ethyl propiolate to the N,0-diformyl derivative (1) of (-)-4-hydroxy-L-proline, followed by deformylation (Scheme 1). Addition... 

Polymer carriers 4-hydroxy-L-proline In vivo—rats... 

Methanesulfonyl chloride Diethylaluminium chloride Orpholinopropanesulfonic acid buffer Benzyl-a-bromopropionate trans-l-(p-Nitrobenzyloxycarbonyl)-4-hydroxy-L-proline Methanesulfonyl chloride t-Butyldimethylsilyl chloride... 

---